Catalysts for body fluid sample extraction

ABSTRACT

An arrangement for producing a sample of body fluid from a wound opening created in a skin surface at a sampling site includes at least one skin-penetration member having a first end configured to pierce the surface of the skin, and a inner lumen in communication with the first end; at least one actuator operatively associated with the at least one skin-penetration member; and at least one catalyst device configured to cause perfusion of body fluid at the sampling site; wherein the at least one actuator is configured to locate the at least one skin-penetration member so as to obstruct the wound opening while transporting body fluid through the inner lumen. Associated methods are also described.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of, and claims priority pursuantto 35 U.S.C. §120 to, U.S. patent application Ser. No. 11/529,613, whichwas filed on Sep. 29, 2006, which claims priority pursuant to 35 U.S.C.§119 to U.S. Patent Application No. 60/721,966 filed Sep. 30, 2005. Theentire contents of each of these applications are hereby incorporated byreference in this application.

FIELD

The present invention relates to devices, arrangements and methodsinvolving body fluid sampling with the assistance of a catalyst. Incertain embodiments, the present invention is directed to integratedmonitoring and body fluid sampling and monitoring devices and methodsthat permit both digital and alternative-site body fluid sampling andanalysis.

BACKGROUND

In the discussion that follows, reference is made to certain structuresand/or methods. However, the following references should not beconstrued as an admission that these structures and/or methodsconstitute prior art. Applicants expressly reserve the right todemonstrate that such structures and/or methods do not qualify as priorart.

According to the American Diabetes Association, diabetes is thefifth-deadliest disease in the United States and kills more than 213,000people a year, the total economic cost of diabetes in 2002 was estimatedat over $132 billion dollars. One out of every 10 health care dollars isspent on diabetes and its complications. The risk of developing type Ijuvenile diabetes is higher than virtually all other chronic childhooddiseases. Since 1987 the death rate due to diabetes has increased by 45percent, while the death rates due to heart disease, stroke, and cancerhave declined.

A critical component in managing diabetes is frequent blood glucosemonitoring. Currently, a number of systems exist for self-monitoring bythe patient. Most fluid analysis systems, such as systems for analyzinga sample of blood for glucose content, comprise multiple separatecomponents such as separate lancing, transport, and quantificationportions. These systems are bulky, and often confusing and complicatedfor the user. The systems require significant user intervention.

Technology development in the field of self-monitoring of blood glucosehas placed the burden of acquiring sufficient blood for conducting atest on the user of the technology. Historically, diabetics have beentaught to lance their finger tips to produce blood for conducting thetest. Ironically, the fingers are not only one of the most sensitivebody parts to pain, but they also are among the areas of skin that aremost highly perfused with blood. Earlier versions of consumer-orientedself-monitoring products usually required many microliters of blood, andthe finger tips provided a reasonably convenient area to lance thatwould be most likely to produce the required volume of blood.

More recently, some self-monitoring systems offer the option to the userto test at alternate sites such as the palm, forearm, or thigh. Whilethese sites are generally known to be significantly less sensitive tothe pain associated with lancing, the adoption of alternate site testinghas been limited for at least four reasons: (1) only a few meterproducts have been approved by the FDA for testing at alternate sites atthis time; (2) many testers do not know that they can use their deviceat the alternate sites; (3) many testers find it relatively difficult toexpress sufficient blood at the alternate sites to perform a test; (4)data published in medical literature on some of the meters shows thatthere may be a distinct difference between glucose levels measured atalternate sites relative to the finger, particularly when glucose levelsare falling and/or the subject may be hypoglycemic. Consequently, thereis a perception by the medical community that there may be an increasedrisk for delayed or improper treatment by the diabetic if they act onlyon the basis of glucose levels measured from alternate sites. Thus, thefinger lancing site remains the most frequently used test site by far.

Lancing devices and the lancets themselves have also evolved somewhatover the past few decades. Some lancing mechanisms may producerelatively less pain by either (1) projecting the lancet in and out ofthe skin in a more straight path and thus reducing stimulation ofpercutaneous nerves which provide the pain stimulus; and (2) offeringdepth control in the lancing device so that the user may balance theexpression of sufficient blood against the level of pain. Furthermore,lancet manufacturers offer a variety of lancet sizes, lengths, and tipbevel patterns with some companies claiming that their lancet is lesspainful than others.

What remains clear is that the most testers, when lancing at the finger,often must put down the lancing device and apply pressure near thefinger tip in order to produce sufficient blood for the test strip inthe meter. Many instructions for use with conventional meter systemsspecifically prescribe that the user perform this “milking” processbecause without it, many will not spontaneously produce the requiredvolume. Applicants have observed this phenomenon in the use of commonlyavailable commercial sampling and meter systems. In a recent study, whena trained professional lanced the finger tips of 16 volunteer diabeticsubjects at the maximum depth setting on commercially available deviceunder controlled conditions, only 15% of lanced sites spontaneouslyproduced sufficient blood for the meter to accurately measure glucoselevels.

Attempts have been made in the past to take steps toward automation ofthe testing process at alternate sites. Specifically, the Sof-Tact®System offered by Medisense in the early 2000s had the capability totest automatically at alternate sites without any user intervention, butonly after each lancet and test strip had been manually loaded into thedevice. This meter is no longer available on the market.

A device similar to the Soft-Tact® device is disclosed in U.S. PatentApplication Publication No. 2004/0138588 A1. This device attempts tointegrate all the functions required to complete a glucose test into onedevice. This device however still requires the user to load a lancet anda test strip prior to each individual testing event, and fails todescribe a catalyst (i.e.—mechanism to stimulate or enhance expressionof blood from the lanced wound site) that ensures that a sufficientsample is expressed from the wound.

The device is described in U.S. Patent Application Publication No.2005/0010134 A1, and U.S. Pat. No. 6,793,633 B2 uses a spring, or motordriven mechanism, to apply pressure around the target wound area. Fromthe description it appears that the user must insert a new lancet andtest strip assembly for each test.

Another disadvantage with conventional arrangements such as the onesreferenced above is that they involve complex and sometimes ineffectivemechanisms for transferring blood or body fluid from the wound to aremote location for analysis. For example, many conventionalarrangements and techniques utilize a solid lancet for creating a woundin the surface of the skin. After piercing the skin the lancet isretracted and a separate member, such as a tube, is positioned totransfer the blood or body fluid. Alternatively, an absorbent test stripis moved into position, manually or in an automated fashion, so that itabsorbs the sample of blood or body fluid from the wound site. Thesearrangements and techniques are overly complex, and clearly rely uponthe precise positioning of the tube or test strip to transfer the sampleof blood or body fluid. When seeking to automate the sampling process,this precise positioning requires rather complex mechanical arrangementsand controls that must operate under close tolerances. Such complexsystems and arrangements are either costly, unreliable, or both.

Thus, conventional sampling devices and methods are overly reliant uponuser intervention, such as milking, in order to consistently express asufficient quantity of blood from the wound site, or are overly complexand/or lack reliability.

Moreover, while many diabetics continue to test their blood glucoselevels with blood from the finger, testing at the alternate sites offersthe advantage of significantly less pain when lancing the palm, forearm,etc. Thus, it would be advantageous to have an automatic and fullyintegrated meter constructed for sampling and/or testing at either thefinger and the alternate sites.

SUMMARY OF THE INVENTION

According to the present invention, there are provided body fluidsampling and monitoring devices and methods that may address one or moreof the shortcomings noted above associated with conventional systems anddevices. According to the present invention, there may also be providedimproved body fluid sampling and monitoring devices and methods thatenable both digital and alternative-site body fluid sampling withoutsignificant user intervention.

As used herein “digital” means fingers or toes. “Digital body fluid”means expression of body fluid from a wound created on the fingers ortoes, and encompasses lancing sites on the dorsal or palm side of thedistal finger tips.

As used herein “alternate site” means a location on the body other thanthe digits, for example, the palm, forearm or thigh. “Alternate-sitebody fluid sampling” means expression of body fluid from the lancingsite on a surface of the body other than the fingers or toes, andencompasses lancing sites on the palm, forearm, and thigh.

As used herein, “body fluid” encompasses whole blood, intestinal fluid,and mixtures thereof.

As used herein “integrated device” or “integrated meter” means a deviceor meter that includes all components necessary to perform sampling ofbody fluid, transport of body fluid, quantification of an analyte, anddisplay of the amount of analyte contained in the sample of body fluid.

As used herein, the term “obstructed opening” means that the needle orskin piercing element is not retracted prior to extracting the bodyfluid from the wound created thereby. Thus, for example, the portion ofthe opening or wound on or just below the surface of the skin is atleast partially obstructed by the skin piercing member or needle whichwill be located at the wound opening entrance on or just below thesurface of the skin upon extraction of body fluid. This aspect of thepresent invention is believed to run counter to the conventional wisdomin the art. See, for example, U.S. Pat. No. 6,063,039.

According to one aspect, the present invention is directed to anarrangement for producing a sample of body fluid from a wound openingcreated in a skin surface at a sampling site, the arrangementcomprising: at least one skin-penetration member having a first endconfigured to pierce the surface of the skin, and a inner lumen incommunication with the first end; at least one actuator operativelyassociated with the at least one skin-penetration member; and at leastone catalyst device configured to enhance perfusion of body fluid at thesampling site;

wherein the at least one actuator is configured to locate the at leastone skin-penetration member so as to obstruct the wound opening whiletransporting body fluid through the inner lumen.

According to another aspect, the present invention is directed to amethod of sampling body fluid from a wound opening created in a skinsurface at a sampling site, the method comprising: automatically ormanually initiating a testing sequence; applying a catalyst to thesampling site; actuating a skin-piercing member so as to drive themember into the surface of the skin thereby creating the wound opening;allowing the at least one skin-penetration member to obstruct the woundopening; and transporting body fluid through an inner lumen of theskin-penetration member; wherein the catalyst is applied to the samplingsite at one or more of the following times: prior to actuating theskin-piercing member, during actuation of the skin-piercing member, orafter actuating the skin-penetration member.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

The following description of preferred embodiments can be read inconnection with the accompanying drawings in which like numeralsdesignate like elements and in which:

FIG. 1 is a partial perspective view of an arrangement constructedaccording to the present invention.

FIG. 2 is a partial cut away side view of the arrangement of FIG. 1.

FIG. 3 is a partial cut away side view of the arrangement of FIG. 1,with an activated catalyst.

FIG. 4 is a partial cut away magnified side view of the arrangement ofFIG. 1, with an activated catalyst and illustrating a mechanism of bodyfluid collection and transport according to the present invention.

FIG. 5 is a perspective view of a portion of an arrangement, includingan actuator, constructed according to the present invention.

FIG. 6 is a perspective view of an integrated device formed according toone embodiment of the present invention.

FIG. 7 is a partial side view of the integrated device of FIG. 6.

FIG. 8 is a perspective view of a component of the integrated device ofFIG. 6.

FIG. 9 is a partial perspective view of various components of theintegrated device of FIG. 6.

FIG. 10 is a side view illustrating various additional components of thedevice of FIG. 6.

FIG. 11 is a perspective view of an integrated device formed accordingto an alternative embodiment of the present invention.

DETAILED DESCRIPTION

According to a first aspect of the present invention, there are providedarrangements and techniques for reliably expressing body fluid from adigit or from an alternate site. For example, according to the presentinvention, arrangements and techniques are provided which consistentlyand reliably express an amount of body fluid that is sufficient toperform an analysis to quantify the amount of an analyte (e.g., glucose,bilirubin, alcohol, controlled substances, toxins, hormones, proteins,etc.) contained therein.

One embodiment of an arrangement 10 of the type described above isillustrated in FIGS. 1-4. As illustrated therein, the arrangement 10 mayinclude a housing 12. The housing 12 may have any suitable shape orconfiguration, and is not limited to the shape and configurationillustrated. The housing 12 can be constructed of any suitable material.For example, the housing 12 may be constructed of a polymeric ormetallic material.

The arrangement 10 may further include a catalyst to assist in thesample acquisition process by enhancing perfusion of blood or body fluidat a sampling site. At least one of several catalysts may be utilized orincluded in the arrangement of the present invention. Possible catalystsinclude, lancing velocity, heat, pressure, vacuum, vibration, andtopical drugs (which induce vasodilatation and increases the blood orbody fluid available at the lancing site). These catalysts may beapplied before, during, after lancing, or in combination with some orall three to facilitate expression of sufficient quantity of body fluidfor determination of the concentration of an analyte contained therein(e.g., glucose).

Lancing velocity refers to the speed at which the skin piercing memberis driven. Velocities ranging from ˜0-22 m/s are possible. Both pain andblood production may increase as velocity increases. Attempts to balancepain and blood have led to a preferred range of about 3-20 m/s, 3-10m/s, or 10-12 m/s.

Pressure is another possible catalyst. Footprint contact pressure can bevaried by a number of possible techniques. One such technique is to varythe size of the opening of the footprint. Another form of pressurecatalyst can take the form of a pressure-applying member thatcircumferentially surrounds and squeezes the digit or other body partfrom which a sample is to be acquired. One illustrative example of thisform of catalyst is a pressure-applying cuff-like member of the typedescribed in U.S. patent application Ser. No. 11/510,784, entitled BODYFLUID MONITORING AND SAMPLING DEVICES AND METHODS, the entire content ofwhich is incorporated herein by reference. The above-described pressurecatalyst can be utilized alone, or in combination with other catalystssuch as vacuum pressure.

Heat is another optional catalyst. Increasing heat, thereby increasingthe skin temperature at the wound site, increases blood productionPossible implementations of heat include IR lights, or resistiveelements to heat the skin.

Another catalyst is vacuum pressure. According to certain embodiments, alight vacuum (e.g., 3-8 in. Hg) is applied to the wound site before,during, and/or after lancing. Several embodiments for applying vacuum tothe wound site are contemplated. One embodiment uses a motor driven pumpto apply vacuum. Alternative embodiments include using individuallypackaged vacuum chambers to apply vacuum, or using a rigid syringe likemechanism to apply vacuum. Other systems use motor driven pumps andsyringes.

According to the principles of the present invention, one or more of theabove-described catalysts can be used in combination with each other,either concurrently or sequentially.

In certain specific embodiments of the arrangement 10, a catalyst device14 can be included which comprises a member or combination of membersfor applying pressure to a surface of the skin S disposed at a locationwhich is proximate to an area from which a sample of body fluid is to beexpressed (i.e., sampling site 28). The catalyst device 14 may cause thearea of the skin from which the sample of body fluid is to be expressedto become perfused with blood and/or body fluid. This effect facilitatesexpression of body fluid from a wound opening 30. According to theillustrated embodiment, the catalyst device 14 comprises a member orcombination of members, such as the illustrated pump 16 and relatedcontroller 18.

The arrangement 10 further comprises a footprint 20 which is attached tothe housing 12. According to the illustrated embodiment, a digit D isplaced on the footprint 20 at the sampling site. However, it should beunderstood that the footprint may also be applied to the surface of theskin at an alternate site. The footprint 20 has a central opening andmay optionally have an annular in shape. However, the footprint is notlimited to this shape or configuration. Numerous shapes orconfigurations may satisfy the function of providing a footprint aroundthe site from which body fluid is to be expressed. The footprint canhave an opening of any suitable diameter or major dimension 21.According to an illustrative example, the diameter or major dimension isat least about 3-8 mm. According to certain embodiments, the footprint20 is constructed from a material which facilitates the formation of aseal between the digit D and the footprint 20. For example, suitablematerials for this purpose include a relatively soft elastomericmaterial, such as a silicone rubber.

The arrangement 10 further includes at least one skin penetration member22. The at least one skin penetration member 22 can take any suitableform. For example, the at least one skin penetration member can comprisea solid lancet or a hollow needle. Conventional arrangements oftenrequire separate mechanisms for drawing a sample of blood to the surfaceof the skin and for transporting the sample to a reaction chamber. Thedevice of the present invention can use a skin-piercing element in theform of a hollow needle to both create and transport the sample, therebygreatly simplifying and improving the effectiveness of the arrangement10. According to one optional embodiment, the skin-penetration member(s)22 can be in the form of a so-called “microneedle.” As the name implies,microneedles are characterizable by their relatively small outerdiameters. For example, a microneedle, as the term is utilized herein,may encompass a skin-penetration member having an outside diameter whichis on the order of 40-200 μm. The inside diameter can vary, for example,having an inside diameter on the order of 25-160 μm. Needles are alsocharacterizable in the art by reference to the “gage.” By way ofillustration, and consistent with the above description, microneedleshaving a gage ranging from 26-36 are clearly comprehended by the presentinvention. Certain advantages may be gleaned from the use of suchmicroneedles as the skin-penetration member. In particular, due to theirsmall size, the size of the wound left upon entry into the skin isrelatively small, thereby minimizing the pain associated with suchneedle insertions and allowing for a quicker healing process. However,the present invention is certainly not limited to the use of suchmicroneedles. Thus, for example, according to one possible alternativeembodiment, the skin penetration member(s) comprise hollow needleshaving a gage of about 20-25, or comprising hollow needles having aninner diameter of about 0.007 inches and an outer diameter of about0.020 inches.

The at least one skin-penetration member 22 can be formed of anysuitable material, such as metal, plastic, glass, etc. Optionally, theat least one skin penetration member can be mounted to a hub 24. Infurther alternative embodiments, the hub 24 may contain an assay pad 34comprising a reagent that changes color upon reaction with a targetanalyte, as known per se to those skilled in the art. As illustrated,for example, in FIG. 2, the skin-penetration member 22 and hub 24 may belocated within a chamber 25. The chamber 25 is in communication withpump 16 so that vacuum pressure can be applied within the chamber 25.The arrangement 10 can comprise a plurality of skin penetration members22. According to certain embodiments, the plurality of skin penetrationmembers 22 can be provided in the form of a replaceable cartridge. Theat least one skin penetration member 22, and/or the hub 24 are attachedto an actuation element 26. The actuation element 26 can take anysuitable form. For example, the actuation element 26 may comprise amechanical, electrical or pneumatic element. According to theillustrated embodiment, the actuation element 26 is in the form of amechanical spring, more specifically, in the form of a torsional spring.

According to certain embodiments of the present invention, the catalystdevice 14 operates in an automatic or semi-automatic manner. Forexample, a user may place the footprint 20 over a surface of the skin ona digit D, or at an alternate site. When the user is ready to produce asample of body fluid, the button B is pressed. This can initiate aprogrammed sequence of events in the device including actuation of thecatalyst device 14, thereby applying vacuum pressure to the skin an areaproximate the tip region of digit D or alternate sampling site (FIG. 3)for a predetermined period of time. The skin-penetration member 22 canthen be driven into the skin (FIG. 4). At a predetermined time, thecatalyst device 14 is deactivated. This mode of operation can becharacterized as “semi-automatic” in that sequence of events must bemanually initiated by the user via pressing the button B.

According to one alternative, the mode of operation can be fullyautomatic. For example, the user places a tip region of digit D on thefootprint 20, or places the footprint over an alternate site. Thearrangement 10 can be provided with one or more sensors 27 that detectand verify that the footprint is properly located and ready for thesampling procedure to begin. Once this state has been sensed, the deviceautomatically activates the catalyst 14 which is applied to the skin atthe sampling site 28 (FIG. 3) for a predetermined period of time.Subsequently, the at least one skin penetration member 22 is driven intothe skin (FIG. 4). At a subsequent predetermined time, the catalystdevice 14 is deactivated. The catalyst device can be deactivated before,during or after the skin-piercing member is driven into the skin.

The arrangement 10 can form at least part of a device which functionsonly to sample body fluid. For example, the arrangement 10 can be usedto express body fluid from the skin in the form of a drop of blood whichpools on the surface of the skin of the user This drop of blood can thenbe transferred to another separate device which then transports and/oranalyzes the sample for a target analyte. Alternatively, the arrangement10 may express a sample of body fluid from the skin, and then transportthe sample to a location which can then be accessed for further analysisby a separate device. For instance, the sample body fluid can betransported to a reagent-containing pad 34, also contained within thearrangement 10. The sample then reacts with the reagent to produce adetectable spot or signal. The reagent pad can then be analyzed by aseparate meter using photochemical, electrochemical, or other suitabletechniques known per se to those skilled in the art. The reagent pad canremain within the arrangement 10 during the aforementioned analysis.According to an alternative embodiment, the reagent pad 34 can beanalyzed by a detector 36 that forms part of the arrangement 10.Alternatively, the reagent pad can be removed from the arrangement 10and inserted into a separate device, such as an electrochemical orphotometric meter.

As illustrated, for example, in FIG. 4, according to this optionalaspect of the present invention a skin-piercing member 22 in the form ofa needle having a first end 22 e configured to pierce the skin and aninner lumen 22 l is driven into the skin to create a wound opening 30therein for producing a sample of body fluid 32, preferably blood. Theneedle is not retracted right away, instead it is allowed to dwell andobstruct the opening 30 created in the surface of the skin. Blood orbody fluid 32 is then extracted and flows through the inner lumen 22 lof the needle, and is eventually transported to a site within thearrangement 10 for further analysis. The blood or body fluid 32 is drawnthough the inner lumen by any suitable mechanism, such as capillaryaction, vacuum, or a combination of both. The needle 22 may be caused todwell at the desired location via any of the mechanisms describedherein. The skin-piercing member 22 is eventually retracted (see, e.g.,FIG. 2). It has been surprisingly observed that an adequate samplevolume can be extracted by the above-described arrangement/technique,especially when utilizing a vacuum catalyst. This arrangement andtechnique is advantageous in that a skin piercing member 22 may be usedfor wound creation and sample transport. Complex mechanisms andarrangements for repositioning a transport member or assay pad to alocation that does not obstruct the opening can be avoided. Otheradvantages of obstructed opening sampling is realizing a reduction inthe required sample volume, and improving the reliability of obtainingan adequate sample. When the needle is located so as to obstruct thewound opening, the end of the needle is closer to the source of bodyfluid, thus smaller drops of sample are more likely to reach the innerlumen of the needle and be successfully transported as the needle restson or in the skin. By contrast, when the needle is withdrawn away fromthe surface of the skin, as in conventional arrangements and techniques,the droplet of blood or body fluid must be significantly larger/tallerto reach the end of the needle and lumen, thereby elevating the riskthat an insufficient sample is obtained.

As illustrated in FIG. 5, each individual skin-piercing element 22 isprovided with its own actuation element or torsional spring 26. Thetorsional spring elements 26 may be provided to the user in a pre-cockedposition. The arcuate acceleration path of the skin-piercing element orneedle 22 may begin up to 180 degrees from the angle of impact with theskin S of the user. According to one beneficial aspect, the pivot pointof the torsional spring elements can be provided as close as possible tothe plane lying on the surface of the skin S in order to ensure that theskin piercing element 22 strikes the skin at an angle which is as closeto 90 degrees as possible. The torsional spring element 26 can act as aguide for the skin-piercing element or needle 22 that locates the tip 22e thereof so as to obstruct the wound opening 30 so as to draw the blood32 into the lumen 22 l of the needle. In this regard, the torsionalspring element 26 may be designed such that its neutral position Ro willlocate the needle so as to obstruct the wound opening 30 created by theskin piercing operation.

Another advantage of this optional aspect of the present invention isthat the torsional spring elements 26 do not require a positive stop tolimit the penetration depth of the skin-piercing element 22. It has beenobserved that elimination of a hard stop may provide certain beneficialeffects. Namely, it has been observed that devices that include a hardstop experience a shock and resulting vibration and/or stirring actionwhen the stop is impacted. It is theorized that this motion may increasethe observable wound and/or the perceived pain associated with sampling.According to this embodiment, the depth of penetration of theskin-penetrating member 22 is determined by a number of factors,including the design of the sharp, the actuation force and the skin'sresistance to penetration at the chosen sampling site. The lack of apositive stop has not been observed as increasing pain in clinicalstudies.

An exemplary body fluid sampling method or technique which may be usedin conjunction with any of the above-described arrangements, but is notnecessarily limited thereto, is described as follows.

A footprint is placed over a sampling site located on a digit or at analternate site. The footprint has an opening therein which defines thesampling site. A sequence of events is then initiated. The events can beinitiated manually, for example, by pressing a button or othertriggering mechanism. Alternatively, the events can be automaticallytriggered, for example, through the use of sensors which determine whenthe footprint has been property positioned over a sampling site on thesurface of the skin. A catalyst is then applied to the sampling site.The catalyst can comprise one or more of lancing velocity, heat,pressure, vacuum, vibration, topical drugs, or combinations thereof.These catalysts can be applied concurrently or sequentially relative toone another. According to one embodiment, a catalyst in the form ofvacuum pressure is applied to the sampling site via a suitablemechanism, such as a pump capable of creating vacuum pressure. Thecatalyst can be applied for a set period of time, and then removed orterminated. For example, the catalyst can be removed before, during, orafter penetration of the skin. Next, at least one skin penetrationmember is actuated or driven into the surface of the skin. The skinpenetration member can take any suitable form, such as a solid lancet orhollow needle (e.g., a microneedle). According to one embodiment, atleast one skin penetration member comprises a hollow needle having afirst end configured to pierce the surface of the skin, and an innerlumen. The at least one skin penetration member can be actuated via anysuitable mechanism, such as a mechanical spring. According to oneoptional embodiment, the actuating mechanism comprises a torsionalspring. The at least skin penetration member is caused to dwell at orbelow the surface of the skin in the vicinity of the wound opening inorder to obstruct the same. The skin penetration member can be caused todwell at this location via any suitable mechanism. According to oneembodiment, the actuator is provided in the form of a torsional springhaving a resting position which can be utilized to cause the first endof the at least one skin penetration member to obstruct the woundopening subsequent to piercing the surface of the skin. During theperiod of time in which the at least one skin penetration member iscaused to dwell at the wound opening, body fluid is transported awayfrom the wound site via a suitable mechanism. According to oneembodiment, the body fluid, or blood, is transported via the inner lumenof a hollow skin-penetration member via capillary action, vacuum, or acombination of both. According to one optional embodiment of the presentinvention, a mechanism can be provided which estimates the acquiredsample volume, and compares this measured sample volume with a targetsample volume. The information acquired by this analysis can be used tocontrol the catalyst such that it is automatically removed once thetarget sample volume has been acquired. Any suitable mechanism can beutilized to analyze the acquired sample volume. For example, the bodyfluid can be transported to an assay pad which contains a chemicalreagent impregnated therein. Upon exposure to the body fluid, a targetanalyte contained therein causes a chemical reaction producing a colorchange in the assay pad. This color change can in turn be detected by asuitable detection element. One such detection element utilizescolorimetric optical analysis of the assay pad. More specifically, anarray of such detection elements can be provided along a longitudinallength of the assay pad. The number of detection elements containedalong the length of the assay pad that detect the presence of the samplecan be correlated to the acquired sample volume. For example, thefurther the sample volume travels along the length of the assay pad thegreater the acquired sample volume. Once it has been determined that atarget sample volume has been acquired, the catalyst can then beterminated. This can be accomplished by the use of a controller insignal communication with a pump. The controller operates based onsignals derived from the analysis of the sample volume in the mannerdescribed above. Some advantages of monitoring volume to activelycontrol the application of the catalyst include reduction in expressionof excess blood or body fluid thereby reducing mess, preventing damageto skin (bruising, etc) due to prolonged catalyst application, andreduction in power consumption.

According to a further optional aspect of the present invention, theabove-described arrangements and methods can form at least part of anintegrated device or integrated meter. As previously noted, as usedherein, the term “integrated device” or “integrated meter” means adevice or meter that includes all components necessary to performsampling of the body fluid, transport of the body fluid, quantificationof an analyte, and display of the amount of analyte contained in thesample of body fluid. Thus, according to the principles of the presentinvention, an integrated device or meter can comprise one or more, orany combination, of the features previously described herein. Accordingto further aspects of the present invention, and integrated meter ordevice can comprise components and/or features in addition to thosespecifically described herein.

An exemplary integrated meter is illustrated in detail in FIGS. 6-10. Asillustrated therein, the integrated meter 100 generally comprises ahousing 112 and a catalyst device 114 (e.g., FIG. 10). The catalystdevice 114 may take any suitable form and can comprise any of thepreviously described alternative catalyst devices. The integrated meter100 may further comprise a footprint 120 of the type previouslydescribed. A door 123 can be provided on the housing 112. The door 123is connected via a hinge 125 to the housing 112. As described in furtherdetail below, the door 123 can be opened to reveal a cartridge 131containing a plurality of skin-piercing elements 122. In the illustratedembodiment, the integrated meter 100 further includes a display 127 forcommunicating the results of the analysis on the sample body fluid forthe presence and/or concentration of an analyte contained therein. Theintegrated meter 100 may further include one or more buttons 129 whichcan be pressed by the user to engage various functions and interfaces ofthe integrated meter 100.

FIG. 7 is an illustration of the integrated meter 100 with the door 123opened to reveal further details of the interior components of theexemplary integrated meter 100. As illustrated therein, the housing 112contains a cartridge 131 therein. In the illustrated embodiment, thecartridge 131 is circular and contains a plurality of skin-piercingelements as further described herein. The cartridge 131 is mounted abouta hub 133 and is rotatable. Thus, upon sampling a skin-piercing element22 is driven through an opening in the housing in registry with thefootprint 120 and pierces the skin of the user. Once the test has beencompleted, the cartridge 131 can be rotated such that an unusedskin-piercing element now comes into registry with the opening in thehousing and the corresponding opening in the footprint 120 inpreparation for the next sampling event. It should be understood thatthe present invention is not limited to the illustrated circularcartridge having the particular configuration depicted in the drawingfigures. To the contrary, a number of alternative cartridgeconfigurations are possible, such as a slidable linear or polygonalconfiguration (not shown). Also illustrated in FIG. 7 is the presence ofa light source 139 disposed on the back of the door 123. The lightsource 139 can take any suitable form, such as a light emitting diode.It should be understood that alternative light sources may also beutilized. The function of the light source 139 will be described infurther detail below.

Further details of the optical assembly 135, the light source 139, andthe replaceable cartridge 131 are illustrated in FIGS. 8-9. Asillustrated therein, the replaceable cartridge 131 generally maycomprise a plurality of compartments defining a plurality of body fluidsampling and analysis sites 132. Contained in each sampling and analysissite 132 is a skin penetration member 122. Each skin penetration member122 can take any suitable form. According to the illustrated embodiment,each skin penetration member 122 is in the form of a hollow needle. Itshould be understood that alternative skin penetration members may alsobe utilized consistent with the principles of the present invention(e.g., solid lancets, etc.) each skin-penetration member can be attachedto a needle hub 124. Each needle hub 124 is, in turn, attached to anactuation element 126. It should be understood that a number ofdifferent actuation elements may be utilized according to the principlesof the present invention. The actuation elements can be mechanical,electrical, pneumatic, etc. According to the illustrated embodiment, theactuation element 126 is in the form of a torsional spring and may havethose features and characteristics previously described herein. Uponactivation, the torsional spring drives the needle hub 124 and theattached skin penetration member 122 into the skin of the user disposedon the footprint 120. According to certain embodiments, eachsampling/analysis site 132 further contains a signaling mechanism whichproduces a detectable signal when contacted with a target analytecontained in a sample of body fluid expressed from the skin. A number ofsuitable mechanisms are envisioned. The mechanisms may be based ontechnologies such as photometric or electrochemical analysis. Accordingto the illustrated embodiment, each needle hub 124 contains a reagentpad 129 which generally comprises an absorbent material containing achemical reagent which, upon reaction with a target analyte, produces achemical reaction that results in a detectable signal. The reagent pad129 is in fluid communication with the inner lumen of the skin piercingelement 122. As noted above, the signal can be detected optically,electrochemically, or by other suitable means. According to oneembodiment, the reagent pad 129, upon reaction with the target analyte,produces a spot which is optically detected by the optical assembly 135in a manner generally known to those skilled in the art. The spotproduced by the above-mentioned reaction can be observed opticallythrough a window 143 formed along the interior region of the illustratedcartridge 131 by the optical assembly 135. In this regard, light emittedfrom the light source 139 is incident upon the reagent pad 129, andreflects off the surface thereof. Upon formation of a reaction spot onthe surface of the reagent pad 129, the amount of light reflected offthe reaction spot differs from the light reflected off of other portionsof the reagent pad 129 containing no such reaction spot. This reflectedlight is picked up by the optical assembly, first through the lens 137(FIG. 7), and eventually is incident upon an optical detector element142 (FIG. 9).

The optical detector element 142 generally comprises one or moredetector elements. According to one alternative construction, thedetector element 142 comprises a plurality of detector elements formedin an array. The array can take any suitable configuration, and can be alinear array or an area array according to one nonlimiting example. Thedetector elements can comprise any suitable construction. For example,the detector elements 142 can comprise a photo diode, CCD, or CMOS baseddetector element. The signals transmitted to the detector element 142are passed on to suitable electronics contained within the housing 112(see, e.g., FIG. 10) via suitable electrical connectors, such asflexible ribbons 141. The specifics of the electronics and signalinterpretation being familiar to those of ordinary skill in the art.While not necessary to enable practice of the presently claimedinvention, further details concerning the structure, function, andarrangement of the optical assembly 135, and the components containedtherein, can be gleaned from the disclosure contained in U.S. PatentApplication Publication No. 2006/0281187, entitled ANALYTE DETECTIONDEVICES AND METHODS WITH HEMATOCRIT/VOLUME CORRECTION AND FEEDBACKCONTROL, the entire content of which is incorporated herein byreference.

Additional components of an integrated meter 100 are illustrated in FIG.10. The view depicted in FIG. 10 is that of an integrated meter 100 withthe back panel removed to reveal the above-referenced additionalcomponents. For example, as illustrated in FIG. 10, the integrated meter100 may further include a plurality of rollers 147 which cooperate withthe cartridge 131 and a motor drive 149 thereby enabling the rotation ofthe cartridge 131 about the hub 133, and indexing of the analysis sites132 with the footprint 120. The integrated meter 100 may also include acatalyst device 114 comprising a pressure pump 151 which, according tocertain embodiments, comprises a pump capable of producing at least anegative or vacuum pressure at the surface of the skin located over thefootprint 120. The integrated meter 100 may further include appropriateelectronics, as embodied in the circuit board 153 of the illustratedembodiment. Preferably, the circuit board contains conventionalelectronic components capable of controlling the various functions ofthe integrated meter 100 in the desired manner, including the pump 151.The particulars of the circuit board 153 and electronic componentsdisposed thereon, being well-known to those of ordinary skill in theart. The integrated meter 100 may further comprise a suitable powersupply 155, such as the illustrated batteries.

As evident from FIGS. 6-10, the integrated meter 100 is configured forhandheld use. However, the invention is not limited to handheld devices.For example, the present invention is also directed to integrated metersthat are wearable. An example of such a wearable device is illustratedin FIG. 11. The wearable integrated device 200 illustrated therein canbe generally composed of a functional portion 202 and a body-attachmentportion 204. The functional portion can comprise an arrangement 10 ofthe type described herein. The functional portion can also have one ormore of the features and elements of the handheld integrated meterdescribed above.

According to further aspects of the present invention, modified devicesand techniques are provided which permit both digital body fluidsampling and analysis as well as alternate-site body fluid sampling andanalysis, which may be performed at the election of the user. In thedescription that follows, it should be understood that the integratedmeters described herein may have any of the features and/or modes ofoperation than that of the previously described embodiments. Forexample, the integrated meter that incorporate arrangements of thepresent invention can include features that facilitate use on digits aswell as alternate sites, at the election of the user. Such features aredescribed in U.S. patent application Ser. No. 11/510,784, entitled BODYFLUID MONITORING AND SAMPLING DEVICES AND METHODS, the entire content ofwhich is incorporated herein by reference.

An exemplary body fluid sampling and analysis methodology or technique,which may be utilized in conjunction with any of the above-mentionedcatalyst devices or integrated meters, but is not necessarily limitedthereto, is described as follows.

A user loads a fresh disposable cartridge containing a plurality of skinpenetration members and analysis sites into an integrated meter. Theintegrated meter then reads calibration data contained in or on thecartridge. This data can be read in any suitable manner. For example, abar code may be placed on the cartridge which can be optically read bythe optical assembly contained within the meter. The integrated meterthen selects the proper lookup table or algorithm to calculate anaggregate glucose measurement taking into consideration the calibrationdata. The meter may then place itself in a ready mode waiting for atrigger to initiate sampling and testing. The user then either manuallypresses a button or trigger to initiate sampling and analysis, or thedevice verifies that it is properly positioned on the skin of the userand ready to begin the sampling and analysis procedure. Suitable sensorsto accomplish this include optical, capacitive or pressure sensors. Thedevice then initiates a catalyst which acts to facilitate the expressionof body fluid. Alternatively, the catalyst is vacuum pressure whichgenerates suction at the sampling site. Optional sensors present in themeter may be used to monitor and control the positive or negativepressure of the catalyst. After achieving a target pressure for adesired period of time, the skin penetration member (e.g., a hollowneedle) is actuated and driven into the skin of the user to create awound site. The skin penetration member comes to rest in or directly onthe wound opening created at the sampling site where it obstructs thewound opening and is in the desired position for collecting a sample ofbody fluid expressed from the wound. The integrated meter may furtherinclude a mechanism for detecting a whether a sufficient amount ofsample has been expressed. Details of such suitable detection techniquesare described in detail in U.S. Pat. No. 7,052,652, entitled ANALYTECONCENTRATION DETECTION DEVICES AND METHODS, the entire content of whichis incorporated herein by reference. Once the desired amount of bodyfluid has been obtained, the catalyst is deactivated. A sample of bodyfluid is in fluid communication with a device or mechanism which createsa detectable signal upon reaction within analyte present in the samplebody fluid. For example, one such suitable mechanism is an absorbent padcontaining a chemical reagent which, upon reaction with the analyteproduces a reaction spot which can be optically detected. An opticalassembly which is in optical communication with the above describedsignal generating mechanism is utilized to detect the signal created viareaction with the analyte and communicate the signals to supportingelectronics contained within the meter. The concentration of a targetanalyte (e.g., glucose) can then be calculated using these signals as abasis. Additional factors may be considered during these calculations,such as the sample size, levels of other substances contained in thesample (e.g. hematocrit), etc. Such optional calculation techniques aredescribed in further detail in U.S. Patent Application Publication No.2006/0281187, entitled ANALYTE DETECTION DEVICES AND METHODS WITHHEMATOCRIT/VOLUME CORRECTION AND FEEDBACK CONTROL, the entire content ofwhich is incorporated herein by reference. These calculations quantifythe amount of analyte contained in the sample body fluid. This quantityis displayed on a suitable display contained within the meter which canbe easily read by the user. The integrated meter then automatically mayretract the skin-penetration member and indexes the disposable cartridgeto present a fresh unused skin penetration member which will be utilizedto perform the next sampling and analysis event.

EXAMPLE

A prototype was constructed using a torsional spring actuator and aneedle designed to position the needle on or in the wound (i.e., toobstruct the wound opening). A vacuum catalyst was also utilized.Results of an evaluation of this prototype are summarized in thefollowing table.

Population Camino Medical Camino Medical Experiment Name PAMF1 PAMF2Actuator Beam Torsional Actuator Version 2.1 5.0 (w/ dwell) # ofSubjects 21  19 Probability BV > 250 nl 94% 93% Probability BV > 300 nl90% 91% Probability BV > 350 nl 85% 85% Average BV (nl) 985 1137

The table shows two experiments for which the lancet design, footprintdesign and footprint contact force were identical. Experiment PAMF1 useda cantilevered beam actuator; this actuator did not allow the needle toremain in or on the wound. Experiment PAMF2 used a torsional coilactuator, this actuator caused the needle to dwell the needle in or onthe skin. Surprisingly, the performance of the torsional coil wascomparable in blood volume (BV) probabilities to the cantilevered beam.Even more surprising was the observation that the torsional coilactually produced a slightly higher average blood volume.

Numbers expressing quantities of ingredients, constituents, reactionconditions, and so forth used in this specification are to be understoodas being modified in all instances by the term “about”. Notwithstandingthat the numerical ranges and parameters setting forth, the broad scopeof the subject matter presented herein are approximations, the numericalvalues set forth are indicated as precisely as possible. Any numericalvalue, however, inherently contains certain errors necessarily resultingfrom the standard deviation found in their respective measurementtechniques. None of the elements recited in the appended claims shouldbe interpreted as invoking 35 U.S.C. §112, ¶6, unless the term “means”is explicitly used.

Although the present invention has been described in connection withpreferred embodiments thereof, it will be appreciated by those skilledin the art that additions, deletions, modifications, and substitutionsnot specifically described may be made without departing from the spiritand scope of the invention as defined in the appended claims.

1. A method for producing a sample of, and for calculating the presenceand/or concentration of a target analyte in, body fluid from a woundopening created in a skin surface at a sampling site, the methodcomprising: providing an arrangement comprising a plurality ofskin-penetration members, the skin penetration members each having afirst end configured to pierce the surface of the skin, and eachskin-penetration member further comprising an inner lumen incommunication with each first end; actuating a first of the pluralityskin-penetration members with a respective torsional spring actuatoroperatively associated with the first skin-penetration member; whereinthe spring actuator has a neutral rest position, and obstructing thewound opening with the first end of the first skin-penetration memberwhen the spring actuator is in the neutral rest position, and urging thefirst skin-penetration member along an arcuate path with the springactuator; applying at least one catalyst to facilitate perfusion of bodyfluid at the sampling site; providing a plurality of signalingmechanisms, each signaling mechanism associated with a respective skinpenetration member, transporting a sample of body fluid from the firstend of the first skin penetration member to a respective signalingmechanism, and generating a detectable signal indicative of the presenceand/or concentration of the target analyte; detecting the signal with atleast one detector associated with the plurality of signalingmechanisms; calculating the presence and/or concentration of the targetanalyte with electronics using the signal; and retracting the firstskin-penetration member after the calculation of the presence and/orconcentration of the target analyte, wherein the arrangement performsthe retracting.
 2. The method of claim 1, further comprising positioninga footprint over the sampling site prior to actuating the skin-piercingmember.
 3. The method of claim 2, wherein the footprint has an opening,the opening having a diameter or major dimension of about 3-8 mm.
 4. Themethod of claim 3, wherein the footprint comprises an elastomeric seal.5. The method of claim 1, wherein the method is initiated by manuallypressing a button.
 6. The method of claim 1, wherein the firstskin-penetration member is actuated and driven into the surface of theskin without interference by a positive stop to limit a depth ofpenetration of the first skin-penetration member.
 7. The method of claim1, wherein applying the catalyst comprises applying one or more ofvacuum pressure, positive pressure, heat, vibration or topical drugs tothe sampling site.
 8. The method of claim 7, wherein applying thecatalyst comprises applying vacuum pressure to the sampling site with apump.
 9. The method of claim 7, further comprising quantifying a volumeof the body fluid sample.
 10. The method of claim 9, further comprisingcontrolling the application of the catalyst based at least in part on avolume of body fluid extracted.
 11. The method of claim 1, furthercomprising providing the plurality of skin-penetration members and theplurality of actuators operatively arranged on a disposable cartridge,and initiating multiple testing sequences without replacing thecartridge.
 12. The method of claim 11, further comprising moving thecartridge to present a new skin-penetration member and actuator for useafter the performance of a preceding testing sequence.
 13. The method ofclaim 2, further comprising sensing when the sampling site is locatedover the footprint.
 14. The method of claim 13, wherein once thesampling site has been sensed, automatically actuating the catalyst andthe first skin penetration member.
 15. The method of claim 1, furthercomprising providing a plurality of hubs, wherein each skin-penetrationmember is attached to a respective hub, and wherein each hub is attachedto a respective torsional spring actuator.
 16. The method of claim 15,wherein each hub comprises a respective signaling mechanism.
 17. Themethod of claim 16, wherein each signaling mechanism comprises a reagentpad.
 18. The method of claim 1, wherein the body fluid comprises blood.19. The method of claim 1, further comprising transporting body fluidthrough the inner lumen of the first skin-penetration member.